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Early prediction of autoimmune (type 1) diabetes

Author:
  • Simon E. Regnell
  • Åke Lernmark
Publishing year: 2017-05-26
Language: English
Pages: 1370-1381
Publication/Series: Diabetologia
Volume: 60
Issue: 8
Document type: Journal article
Publisher: Springer

Abstract english

Underlying type 1 diabetes is a genetic aetiology dominated by the influence of specific HLA haplotypes involving primarily the class II DR-DQ region. In genetically predisposed children with the DR4-DQ8 haplotype, exogenous factors, yet to be identified, are thought to trigger an autoimmune reaction against insulin, signalled by insulin autoantibodies as the first autoantibody to appear. In children with the DR3-DQ2 haplotype, the triggering reaction is primarily against GAD signalled by GAD autoantibodies (GADA) as the first-appearing autoantibody. The incidence rate of insulin autoantibodies as the first-appearing autoantibody peaks during the first years of life and declines thereafter. The incidence rate of GADA as the first-appearing autoantibody peaks later but does not decline. The first autoantibody may variably be followed, in an apparently non-HLA-associated pathogenesis, by a second, third or fourth autoantibody. Although not all persons with a single type of autoantibody progress to diabetes, the presence of multiple autoantibodies seems invariably to be followed by loss of functional beta cell mass and eventually by dysglycaemia and symptoms. Infiltration of mononuclear cells in and around the islets appears to be a late phenomenon appearing in the multiple-autoantibody-positive with dysglycaemia. As our understanding of the aetiology and pathogenesis of type 1 diabetes advances, the improved capability for early prediction should guide new strategies for the prevention of type 1 diabetes.

Keywords

  • Endocrinology and Diabetes
  • Autoimmunity
  • Beta cells, diabetes mellitus
  • Glutamic acid decarboxylase autoantibodies
  • HLA
  • Insulin autoantibodies
  • Insulin secretion
  • Insulinoma-associated antingen-2 autoantibodies
  • Next-generation sequencing
  • Review
  • Type 1 diabetes
  • ZnT8 autoantibodies

Other

Published
  • Diabetes and Celiac Unit
  • ISSN: 0012-186X
E-mail: ake [dot] lernmark [at] med [dot] lu [dot] se

Principal investigator

Diabetes and Celiac Unit

+46 40 39 19 01

+46 70 616 47 79

60:11:015

Jan Waldenströms gata 35, Malmö

33

Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00